The mitochondrial C16069T polymorphism, not mitochondrial D310 (D-loop) mononucleotide sequence variations, is associated with bladder cancer

Background: Bladder cancer is a relatively common and potentially life-threatening neoplasm that ranks ninth in terms of worldwide cancer incidence. The aim of this study was to determine deletions and sequence variations in the mitochondrial displacement loop (D-loop) region from the blood specimens and tumoral tissues of patients with bladder cancer, compared to adjacent non-tumoral tissues. Methods: The DNA from blood, tumoral tissues and adjacent non-tumoral tissues of twenty-six patients with bladder cancer and DNA from blood of 504 healthy controls from different ethnicities were investigated to determine sequence variation in the mitochondrial D-loop region using multiplex polymerase chain reaction (PCR), DNA sequencing and southern blotting analysis. Results: From a total of 110 variations, 48 were reported as new mutations. No deletions were detected in tumoral tissues, adjacent non-tumoral tissues and blood samples from patients. Although the polymorphisms at loci 16189, 16261 and 16311 were not significantly correlated with bladder cancer, the C16069T variation was significantly present in patient samples compared to control samples (p < 0.05). Interestingly, there was no significant difference (p > 0.05) of C variations, including C7TC6, C8TC6, C9TC6 and C10TC6, in D310 mitochondrial DNA between patients and control samples. Conclusion: Our study suggests that 16069 mitochondrial DNA D-Loop mutations may play a significant role in the etiology of bladder cancer and facilitate the definition of carcinogenesis-related mutations in human cancer.

via Cancer Cell International

Anti-CCR7 therapy exerts a potent anti-tumor activity in a xenograft model of human mantle cell lymphoma

Background: The chemokine receptor CCR7 mediates lymphoid dissemination of many cancers, including lymphomas and epithelial carcinomas, thus representing an attractive therapeutic target. Previous results have highlighted the potential of the anti-CCR7 monoclonal antibodies to inhibit migration in transwell assays. The present study aimed to evaluate the in vivo therapeutic efficacy of an anti-CCR7 antibody in a xenografted human mantle cell lymphoma model. Methods: NOD/SCID mice were either subcutaneously or intravenously inoculated with Granta-519 cells, a human cell line derived from a leukemic mantle cell lymphoma. The anti-CCR7 mAb treatment (3 x 200 mug) was started on day 2 or 7 to target lymphoma cells in either a peri-implantation or a post-implantation stage, respectively. Results: The anti-CCR7 therapy significantly delayed the tumor appearance and also reduced the volumes of tumors in the subcutaneous model. Moreover, an increased number of apoptotic tumor cells was detected in mice treated with the anti-CCR7 mAb compared to the untreated animals. In addition, significantly reduced number of Granta-519 cells migrated from subcutaneous tumors to distant lymphoid organs, such as bone marrow and spleen in the anti-CCR7 treated mice. In the intravenous models, the anti-CCR7 mAb drastically increased survival of the mice. Accordingly, dissemination and infiltration of tumor cells in lymphoid and non-lymphoid organs, including lungs and central nervous system, was almost abrogated. Conclusions: The anti-CCR7 antibody exerts a potent anti-tumor activity and might represent an interesting therapeutic alternative to conventional therapies.

via Journal of Hematology & Oncology

Role of the Hypoxia-inducible factor-1 alpha induced autophagy in the conversion of non-stem pancreatic cancer cells into CD133+ pancreatic cancer stem-like cells

The initiation and progression of various solid tumors, including pancreatic carcinoma, are driven by a population of cells with stem cell properties, namely cancer stem cells (CSCs). Like their normal counterparts, CSCs are also believed to rely on their own microenvironment termed niches to sustain the population. Hypoxia-inducible factor-1alpha (HIF-1alpha) is a major actor in the cell survival response to hypoxia. Recently, several researchers proposed that non-stem cancer cells can convert to stem-like cells to maintain equilibrium. The present study focuses on whether non-stem pancreatic cancer cells can convert to stem-like cells and the role of HIF-1alpha and autophagy in modulating this conversation. The non-stem pancreatic cancer cells and pancreatic cancer stem-like cells were separated by magnetic sorting column. Intermittent hypoxia enhanced stem-like properties of non-stem pancreatic cancer cells and stimulated the levels of HIF-1alpha, LC3-II and Beclin. Enhanced autophagy was associated with the elevated level of HIF-1alpha. The conversation of non-stem pancreatic cancer cells into pancreatic cancer stem-like cells was induced by HIF-1alpha and autophagy. This novel finding may indicate the specific role of HIF-1alpha and autophagy in promoting the dynamic equilibrium between CSCs and non-CSCs. Also, it emphasizes the importance of developing therapeutic strategies targeting cancer stem cells as well as the microenvironmental influence on the tumor.

via Cancer Cell International

Lung cancer is costliest cancer in European Union

The total cost of cancer care across the European Union was an estimated € 126 billion in 2009, with lung cancer having the highest cost, at 15% of the total.

via Med Wire News

Investigational c-Met inhibitor shows early promise in NSCLC

A first-in-class drug that inhibits c-Met, a receptor tyrosine kinase, has demonstrated good tolerability when combined with erlotinib in the treatment of Japanese patients with advanced/metastatic non-small-cell lung cancer.

via Med Wire News

Clinicians ‘nihilistic’ toward lung cancer patients

Clinicians tend to view their lung cancer patients more negatively than patients with other solid tumors, study findings indicate.

via Med Wire News

Four-drug regimen shows first-line efficacy in advanced NSCLC

A four-drug combination of cetuximab, bevacizumab, carboplatin, and paclitaxel is effective and has acceptable safety as a first-line treatment for advanced non-small-cell lung cancer, US researchers report.

via Med Wire News